Potassium Phosphate, Tribasic → HCID 86270036, compound

HRID 2279020Notes

Reaction equation

HRID 2279020 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:25])=[CH:11][C:12]([NH:15][C:16]([N:18]3[CH2:22][CH2:21][N:20]([CH3:23])[C:19]3=[O:24])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:26][C:27]1[N:28]=[CH:29][NH:30][CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:23][N:20]1[CH2:21][CH2:22][N:18]([C:16]([NH:15][C:12]2[CH:11]=[C:10]([CH3:25])[C:9]([O:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([N:30]4[CH:31]=[C:27]([CH3:26])[N:28]=[CH:29]4)[CH:7]=3)=[CH:14][N:13]=2)=[O:17])[C:19]1=[O:24]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 90426285HCID 90426285, compoundHCID 178418800HCID 178418800, compound

Product 1

HCID 86270036HCID 86270036, compoundYield 17.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent3×HCID 312751,4-DioxaneSolvent3×

Procedure

A solution of Pd2(dba)3 (10.12 mg, 0.011 mmol) and Me4t-BuXPhos (0.012 g, 0.025 mmol) in toluene (0.2 mL) and dioxane (0.4 mL) was heated at 120° C. for 3 min, cooled to RT, added to a degassed suspension of N-(5-((2-chloropyridin-4-yl)oxy)-4-methylpyridin-2-yl)-3-methyl-2-oxoimidazolidine-1-carboxamide (0.1 g, 0.276 mmol), 4-methyl imidazole (0.030 g, 0.359 mmol) and K3PO4 (0.117 g, 0.553 mmol) in toluene (0.4 mL) and dioxane (0.8 mL) and heated at 110° C. overnight. The mixture was treated with additional catalyst (synthesized from Pd2(dba)3 (10.12 mg, 0.011 mmol) and Me4t-BuXPhos (0.012 g, 0.025 mmol) in toluene (0.2 mL) and dioxane (0.4 mL) as above) and heated at 110° C. overnight. The mixture was cooled to RT, treated with satd. NaHCO3, extracted with EtOAc (5×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM). The material was treated with MeCN, heated to reflux, cooled to RT and the resulting solid collected via filtration and dried to afford 3-methyl-N-(4-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (20 mg, 17%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1 H), 8.39 (d, J=1.4 Hz, 1 H), 8.30 (d, J=5.8 Hz, 1 H), 8.13 (s, 1 H), 8.02 (s, 1 H), 7.64 (t, J=1.3 Hz, 1 H), 7.33 (d, J=2.2 Hz, 1 H), 6.73 (dd, J=5.8, 2.2 Hz, 1 H), 3.79-3.78 (m, 2 H), 3.46-3.44 (m, 2 H), 2.80 (s, 3 H), 2.15 (s, 3 H), 2.13 (s, 3H); MS (ESI) m/z: 408.2 (M+H+).

Workup

  1. temperatureheated at 110° C. overnight
  2. temperatureheated at 110° C. overnight
  3. temperatureThe mixture was cooled to RT
  4. additiontreated with satd
  5. extractionNaHCO3, extracted with EtOAc (5×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified twice via silica gel chromatography (MeOH/DCM)
  9. additionThe material was treated with MeCN
  10. temperatureheated
  11. temperatureto reflux
  12. temperaturecooled to RT
  13. filtrationthe resulting solid collected via filtration
  14. customdried

Sources & evidence

ORD record
ord-59ac0fea3afb45b5ac29306b7640b23a
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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